To the Editor :
At present, it is clear that conventional anti-cancer methods are of little efficiency in people with metastases while the upcoming approach such as gene therapy1 is far from introduction into a broad clinical practice in the near future. Moreover, application even the latest therapeutic strategies2, 3 and radiation techniques4, 5 may result in severe weakness, depression of bone marrow, loss of hair, damage of internal organs and dermatoses6. Therefore, development of news anti-cancer approaches is one of the most important challenges in modern medicine.
Recently, we have reported briefly7 about application of new bacterial-based therapeutic methodology that is able to inhibit metastatic growth and significantly improve the patient’s quality of life. The essence of our method is peroral administration of Bacillus oligonitrophilus KU-1 that has been shown in several observational studies to improve the quality of life of patients with solid cancers. Here we present some additional data on patient with rectal adenocarcinoma who has experienced an exceptional beneficial response to our bacterial-based treatment.
Bacillus oligonitrophilus KU-1 (Bacteria; Firmicutes; Bacilli; Bacillales; Bacillaceae: according to8 strain was isolated from soil of Kazan city. Scheme of administration is presented below.
Patient under study, female, was born in 1937. In November 25, 1998, mild differentiated rectal adenocarcinoma with non-operative metastases into greater omentum was determined (T3N1M1) at Tatarstan Republican Hospital (Kazan, Russia). In November 30, 1998, colonoscopic polypectomy of larger polypus was made. In December 2, 1998, abdominal resection of rectum was made at the same hospital. In December 15, 1998, formation of sigmoid-anal anastomosis was made. Between the operation days, health status was satisfactory and the patient resided in hospital. The overall post-surgical outcome was uneventful. In December 25, 1998, the patient left the hospital.
Since February 1999, peroral administration of B. oligonitrophilus KU-1 stationary phase culture (0.5-1.0x109 cells per mL) was started by the patient according to the following scheme: 1st day: 2.5 mL, 2nd day: 5 mL, 3rd day: 10 mL, 4th day: 20 mL, 5th day: 40 mL, 6th day: 60 mL, 7th day: 80 mL, 8th day: 100 mL, 9th day: 120 mL, 10th day:140 mL, 11th day: 160 mL, 12th day: 180 mL, 13th day: 200 mL and then 200-250 mL per day. In August 1999, regular administration was stopped. Since August 1999 until November 2003, there was only preventive administration during each spring (200-250 mL per day). Since November 2003, regular administration (100 mL per day) of B. oligonitrophilus KU-1 culture was renewed. In March 2004, ultrasonography of liver, kidneys, pancreas and spleen was made (results were without pathology). Gastroduodenoscopy studies revealed polypus (0.6x0.8 cm) in stomach without need to operate. In June 2004, regular administration was stopped. During Spring 2005, she received B. oligonitrophilus KU-1 (100 mL per day, one week of administration followed one week of interruption). In February 2006, ultrasonography of liver, pancreas and spleen was made (results were without pathology). A few cystic lesions were found on the right and left kidney (up to 16 and 12 mm in diameter, respectively). The size of the stomach polypus is without changes since March 2004. Since March 2006, she receives B. oligonitrophilus KU-1 with prophylactic aim. All laboratory findings are shown in Table 1.
This case suggests that peroral administration of B. oligonitrophilus KU-1 could be used for therapeutic and preventive use. Of course, our study has a significant limitation because computed tomography and magnetic resonance tomography data were absent. In this connection, we cannot rule out formation of peritoneal metastasis: this probably took place, in parvo, during increment of CA19-9. In the same time, it is reasonable, however, to suggest that there was no enormous metastatic growth because of good health sense and increased survival (more than 7 years). The patient had a favorable tolerance profile: this probably explains the observed therapeutic success and she had no, for example, gastritis, nausea or retching as it took place in our other patients7. However, patient demonstrated an increased arterial tension (both systolic and diastolic) in 1999 that was elevated approximately on 20 mm of mercury. We presuppose that elevation of arterial tension might be a consequence of the tumor clone inhibition.
According to theoretical prognosis, over 50 000 people will die (only in USA) in 2006 due to colorectal cancer9. This points out an importance of the medical problem. We have to thank conventional chemotherapeutists for their constant efforts to increase tolerance and efficiency of chemotherapeutic drugs by means of various remedy combinations10-12 but, unfortunately, the frequency of relapse and subsequent death remains significant13. Because some lifestyle factors (diet, ataraxy, etc.) were shown to be important in the cancer disease management14-15, we recommend keeping some recommendations: vegetarian diet, administration of probiotics (their preclusive effect was shown in many studies, see for example 16), and prevention of supercooling, superheating and psychic anxieties.
Although some suppositions on the B. oligonitrophilus KU-1 mechanism of action has been made7, 17, it is necessary to perform further research to clarify all possible modes of the observed anti-cancer effect. Moreover, randomized double blind trials are needed to evaluate efficiency of the suggested therapeutic approach in various cancers.
1. Vassaux G, Martin-Duque P. Use of suicide genes for cancer therapy; study of the different approaches. Expert Opin Biol Ther 2004; 4: 519-530.
2. Liscovitch M, Lavie Y. Cancer multidrug resistance: A review of recent drug discovery research. Drugs 2002; 5: 349-355.
3. Folkman J. Endogenous angiogenesis inhibitors. APMIS 2004; 112: 496-507.
4. Alheit H, Saran PH, Warrington AP. Stereotactically guided conformal radiotherapy for meningiomas. Radiother Oncol 1999; 50: 145-150.
5. Bolsi A, Fogliata A, Cozzi L. Radiotherapy of small intracranial tumours with different advanced techniques ultrasonographyng photon and proton beams: a treatment planning study. Radiother Oncol 2003; 68: 1-14.
6. Harper JL, Franklin LE, Jenrette JM, Aguero EG. Skin toxicity during breast irradiation: pathophysiology and management. South Med J. 2004; 97: 989-993.
7. Malkov SV, Markelov VV, Polozov GY, Sobchuk LI, Zakharova NG, Barabanschikov BI, Kozhevnikov AY, Vaphin RA, Trushin MV. Antitumor features of Bacillus oligonitrophilus KU-1 strain. J Microbiol Immunol Infect 2005; 38: 96-104.
8. Krasilnikov NA, eds. Opredelitel bakterii i actinomycetov (Manual for identification of bacteria and actinomycete). Moscow-Leningrad: USSR Academy of Sciences Press; 1949.
9. American Cancer Society. How many people get colorectal cancer? Available at: http://www.cancer.org/docroot/CRI/content/CRI_2_2_1X_How_Many_People_Get_Colorectal_Cancer.asp?rnav=cri. Accessed February 24, 2006.
10. Hoff PM, Pazdur R. Progress in the development of novel treatments for colorectal cancer. Oncology (Williston Park) 2004;18: 705-708.
11. Rougier P, Lepere C. Second-line treatment of patients with metastatic colorectal cancer. Semin Oncol 2005; 32: 48-54.
12. Allegra C, Sargent DJ. Adjuvant therapy for colon cancer-the pace quickens. N Engl J Med. 2005; 352: 2746-2748.
13. Brooks BJ Jr. Clinical update on oncology treatments and trends. Am J Manag Care 2006; 12: S45-70.
14. Wallace JM. Nutritional and Botanical Modulation of the Inflammatory Cascade - Eicosanoids, Cyclooxygenases,and Lipoxygenases - as an Adjunct in Cancer Therapy. Integrative Cancer Ther 2002; 1: 7-37.
15. Cunningham AJ. Group Psychological Therapy: An Integral Part of Care for Cancer Patients. Integrative Cancer Ther 2002; 1: 67-76.
16. Marotta F, Naito Y, Minelli E, Tajiri H, Bertuccelli J, Wu CC, Min CH, Hotten P, Fesce E. Chemopreventive effect of a probiotic preparation on the development of preneoplastic and neoplastic colonic lesions: an experimental study. Hepatogastroenterology 2003; 50: 1914-1918.
17. Malkov SV, Markelov VV, Barabanschikov BI, Trushin MV, Marotta F. Genome rejuvenation and its applications. Biomed Scientist 2006; 50: 45-47.
Dr. Maxim V. Trushin
Kazan Institute of Biochemistry and Biophysics
Lobachevskii str. 2/31, P.O. Box 30,
420111, Kazan, Russia
Received April 3, 2006
Published, April 11, 2006.